Recently, we have demonstrated that remission lymphocytes from acute lymphoblastic leukemia (ALL) patients are able to become cytotoxic to their respective leukemic blasts (ALB) following exposure to ALB, soluble microbial extracts, poly AU, levamisole, or cyclophosphamide. However, there seems to be a variation in the ability of ALB to stimulate and the ability of patients lymphocytes to become cytotoxic. In some cases when ALB alone could not generate cytotoxic lymphocytes the combination of ALB and BCG extract induced greater cytotoxicity than was induced by BCG extract alone. At present, the mechanisms of nonresponsiveness of certain ALL patient's lymphocytes, and efforts to correct and/or potentiate the responsiveness to tumor cells is being investigated. The presence of suppressor cells, lack of helper cell activity, production of prostaglandins, and/or poor immunogenicity of leukemia cells are under investigation as a possible cause of nonresponsiveness of variation in lymphocytes response to leukemia cells. The adherent suppressor cells will be removed by either glass wool column or nylon wool column. Lymphocytes will be fractionated on discontinuous gradient of bovine serum albumin. Tr, Tmu, and Tphi subpopulations of T cells will be separated and their abilities to become cytotoxic or suppress the induction of cytotoxicity will be tested. Effect of thymosin, levamisole, poly AU or cyclophosphamide will be determined on nonresponder lymphocytes. Whether prostaglandins are responsible for the inability of some leukemia cells to stimulate lymphocytes will be studied. Attempts will be made to see whether indomethacin (an inhibitor of prostaglandins synthesis) will restore the ability of remission lymphocytes to become cytotoxic against leukemia cells. The inability of certain leukemia cells to sensitize lymphocytes may be due to poor antigenicity of leukemia cells. Attempts will be made to modify leukemia cells by chemicals (e.g. idoacetamide) or enzymes (e.g. vibrio cholarae neuraminidase) and then their ability to stimulate lymphocytes to become cytotoxic will be determined.